IRCCS Policlinico S. Matteo Foundation, Unit of Clinical Epidemiology and Center for the Study of Myelofibrosis, Viale Golgi 19, 27100 Pavia, Italy.
Expert Opin Pharmacother. 2011 Jul;12(10):1597-611. doi: 10.1517/14656566.2011.568939. Epub 2011 Apr 4.
Myeloproliferative neoplasm (MPN)-associated myelofibrosis is the most disabling of the classical Philadelphia-negative MPNs. The discovery that a gain-of-function mutation of JAK2 (JAK2V617F) is present in more than 60% of patients with MPN-associated myelofibrosis has provided a new target for innovative treatment strategies.
This review discusses the indications and limitations of conventional therapies employed for the treatment of MPN-associated myelofibrosis before reviewing the information available for new therapies, including the immunomodulatory and demethylating agents, histone deacethylase, mammalian target of rapamycin (mTOR) and JAK2- inhibitors. The Medline and ASH databases were searched for clinical trials on the medical therapy of MPN-associated myelofibrosis from early 2000 to December 2010.
Three categories of drugs have proved to have significant activity in MPN-associated myelofibrosis. Up to a 40% response rate on anemia has been reported with the immunomodulator, pomalidomide. The m-TOR inhibitor RAD-001 and various JAK2 inhibitors have documented a profound effect on splenomegaly and constitutional symptoms, with some also having activity on anemia. These new drugs will give physicians more options to tailor therapeutic choice in this challenging disease.
骨髓增殖性肿瘤（MPN）相关的骨髓纤维化是经典费城阴性 MPN 中最具致残性的疾病。在超过 60%的 MPN 相关骨髓纤维化患者中发现存在 JAK2 功能获得性突变（JAK2V617F），为创新治疗策略提供了新的靶标。
本综述讨论了在回顾新治疗方法的信息之前，用于治疗 MPN 相关骨髓纤维化的常规治疗的适应证和局限性，包括免疫调节剂和去甲基化剂、组蛋白去乙酰化酶、哺乳动物雷帕霉素靶蛋白（mTOR）和 JAK2 抑制剂。从 2000 年初到 2010 年 12 月，检索了 Medline 和 ASH 数据库中关于 MPN 相关骨髓纤维化的医学治疗的临床试验。
三类药物已被证明对 MPN 相关骨髓纤维化具有显著疗效。免疫调节剂泊马度胺可使贫血的缓解率达到 40%。mTOR 抑制剂 RAD-001 和各种 JAK2 抑制剂对脾肿大和全身症状有显著疗效，一些药物对贫血也有疗效。这些新药将为医生在治疗这种具有挑战性的疾病时提供更多的治疗选择。
